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深入探究以确定是什么导致DNA损伤具有有害性。

Looking beneath the surface to determine what makes DNA damage deleterious.

作者信息

Greenberg Marc M

机构信息

Department of Chemistry, Johns Hopkins University, 3400N, Charles Street, Baltimore, MD 21218, United States.

出版信息

Curr Opin Chem Biol. 2014 Aug;21:48-55. doi: 10.1016/j.cbpa.2014.03.018. Epub 2014 Apr 22.

Abstract

Apurinic/apyrimidinic and oxidized abasic sites are chemically reactive DNA lesions that are produced by a variety of damaging agents. The effects of these molecules that lack a Watson-Crick base on polymerase enzymes are well documented. More recently, multiple consequences of the electrophilic nature of abasic lesions have been revealed. Members of this family of DNA lesions have been shown to inactivate repair enzymes and undergo spontaneous transformation into more deleterious forms of damage. Abasic site reactivity provides insight into the chemical basis for the cytotoxicity of DNA damaging agents that produce them and are valuable examples of how looking beneath the surface of seemingly simple molecules can reveal biologically relevant chemical complexity.

摘要

脱嘌呤/脱嘧啶位点和氧化脱碱基位点是由多种损伤因子产生的具有化学反应活性的DNA损伤。这些缺乏沃森-克里克碱基的分子对聚合酶的影响已有充分记载。最近,脱碱基损伤的亲电性质的多种后果已被揭示。这类DNA损伤家族的成员已被证明会使修复酶失活,并自发转化为更具有害性的损伤形式。脱碱基位点的反应活性为产生它们的DNA损伤剂的细胞毒性提供了化学基础的见解,并且是看似简单的分子表面之下的研究如何揭示具有生物学相关性的化学复杂性的宝贵例子。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1738/4149920/f2a7cfe80e9b/nihms588818f1.jpg

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